Background. Chronic fatigue has infrequently been studied in twins. Data from twin studies can inform clinical and research approaches to the management and etiology of human complex traits.

Method. The authors obtained telephone interview data on current chronic fatigue from 31406 individuals twins in the Swedish Twin Registry (aged 42–64 years, 75·68% response rate), from both members of 12407 pairs and from one member of 6592 pairs. Of the complete pairs, 3269 pairs were monozygotic, 9010 pairs dizygotic, and 128 pairs of unknown zygosity. Structural equation twin modeling was used to estimate the latent genetic architecture of varying definitions of fatiguing illness.

Results. Estimates of additive genetic effects, shared environmental effects, and individual-specific environmental effects were similar in males and females. No definition of current fatiguing illness (ranging from any fatigue to CFS-like illness) was strikingly distinctive. Individual-specific effects were the predominant source of variation, followed by modest genetic influences. We could not exclude a small but conceptually important contribution of shared environmental effects.

Conclusions. Current fatiguing illness appears to be a complex trait resulting from both environmental and genetic sources of variation without pronounced differences by gender.